Evidence of exposure to Rickettsia felis in Australian patients

AbstractRickettsia felis is an emerging zoonosis, causing flea-borne spotted fever (FBSF). Serological diagnosis is typically confounded by cross-reactivity with typhus group rickettsiae and prior to the development of specific serological methods, cases of FBSF in Australia were misdiagnosed.Patient sera tested between August 2010 and December 2013 and known to be seropositive to R. typhi by immunofluorescence antibody testing (IFAT) were subsequently retested against R. felis using an R. felis-specific IFAT. Sera of 49 patients were of a sufficient quality to be included in re-analysis. A classification of FBSF and murine typhus (MT) was attributed to fourteen and seven patients respectively, based on a minimum four-fold higher antibody titre to R. felis than to R. typhi and vice versa. Twenty-eight patients were classified as indeterminate for either R. felis or R. typhi (antibody titres within two-fold of one another).Historically, it is likely that Australian patients clinically ill with FBSF were misdiagnosed. It is important that medical practitioners consider FBSF as part of their differential diagnoses, and obtain relevant history with regard to patient's exposure to domestic pets and their fleas. Australian microbiology diagnostic laboratories should include serological testing for R. felis as part of the diagnostic panel for febrile diseases. Veterinarians are encouraged to increase their awareness of this emerging zoonosis and advocate flea control in pets

Exposure to Leptospira spp. and associated risk factors in the human, cattle and dog populations in Bhutan

Leptospirosis is a neglected worldwide zoonotic bacterial disease with a high prevalence in subtropical and tropical countries. The prevalence of Leptospira spp. in humans, cattle and dogs is unknown in Bhutan. Therefore, we sought to find out whether humans, cattle or dogs had been infected in the past with leptospires by measuring antibodies in the serum. We therefore collected blood from 864 humans >/=13 years of age, 130 bovines and 84 dogs from different rural and urban areas in Bhutan and tested the serum for antibodies specific for leptospires with a screening of enzyme-linked immunosorbent assays (ELISA) and a confirmatory microscopic agglutination test (MAT). In humans, 17.6% were seropositive by ELISA and 1.6% by MAT. The seropositivity was stronger in bovines (36.9%) and dogs (47.6%). "Having had a fever recently" (OR 5.2, p = 0.004), "working for the military" (OR 26.6, p = 0.028) and "being unemployed" (OR 12.9, p = 0.041) (reference category = housemaker) were statistically significantly associated with seropositivity when controlled for the effects of other risk factors. However, due to the small number of positive test results, the findings on risk factors should be interpreted with caution. Based on the serogroups found in the three species, dogs could be a source of infection for humans, or dogs and humans are exposed to the same environmental risk factors Clinical leptospirosis in humans and domestic animals should be investigated by testing blood and urine for the presence of leptospires by molecular methods (qPCR)

One Health approach to controlling a Q fever outbreak on an Australian goat farm

A recent outbreak of Q fever was linked to an intensive goat and sheep dairy farm in Victoria, Australia, 2012-2014. Seventeen employees and one family member were confirmed with Q fever over a 28-month period, including two culture-positive cases. The outbreak investigation and management involved a One Health approach with representation from human, animal, environmental and public health. Seroprevalence in non-pregnant milking goats was 15% [95% confidence interval (CI) 7–27]; active infection was confirmed by positive quantitative PCR on several animal specimens. Genotyping of Coxiella burnetii DNA obtained from goat and human specimens was identical by two typing methods. A number of farming practices probably contributed to the outbreak, with similar precipitating factors to the Netherlands outbreak, 2007-2012. Compared to workers in a high-efficiency particulate arrestance (HEPA) filtered factory, administrative staff in an unfiltered adjoining office and those regularly handling goats and kids had 5·49 (95% CI 1·29–23·4) and 5·65 (95% CI 1·09–29·3) times the risk of infection, respectively; suggesting factory workers were protected from windborne spread of organisms. Reduction in the incidence of human cases was achieved through an intensive human vaccination programme plus environmental and biosecurity interventions. Subsequent non-occupational acquisition of Q fever in the spouse of an employee, indicates that infection remains endemic in the goat herd, and remains a challenge to manage without source control

The troublesome ticks research protocol: Developing a comprehensive, multidiscipline research plan for investigating human tick-associated disease in Australia

In Australia, there is a paucity of data about the extent and impact of zoonotic tick-related illnesses. Even less is understood about a multifaceted illness referred to as Debilitating Symptom Complexes Attributed to Ticks (DSCATT). Here, we describe a research plan for investigating the aetiology, pathophysiology, and clinical outcomes of human tick-associated disease in Australia. Our approach focuses on the transmission of potential pathogens and the immunological responses of the patient after a tick bite. The protocol is strengthened by prospective data collection, the recruitment of two external matched control groups, and sophisticated integrative data analysis which, collectively, will allow the robust demonstration of associations between a tick bite and the development of clinical and pathological abnormalities. Various laboratory analyses are performed including metagenomics to investigate the potential transmission of bacteria, protozoa and/or viruses during tick bite. In addition, multi-omics technology is applied to investigate links between host immune responses and potential infectious and non-infectious disease causations. Psychometric profiling is also used to investigate whether psychological attributes influence symptom development. This research will fill important knowledge gaps about tick-borne diseases. Ultimately, we hope the results will promote improved diagnostic outcomes, and inform the safe management and treatment of patients bitten by ticks in Australia

Human Infection with Rickettsia honei, Thailand

Human spotted fever rickettsiosis was detected molecularly by 2 real-time polymerase chain reaction (PCR) assays performed on DNA extracted from a Thai patient's serum sample. Sequences of PCR amplicons from 5 rickettsial genes used for multilocus sequence typing were 100% identical with those deposited with GenBank for Rickettsia honei TT-118

Murine Typhus and Febrile Illness, Nepal

Murine typhus was diagnosed by PCR in 50 (7%) of 756 adults with febrile illness seeking treatment at Patan Hospital in Kathmandu, Nepal. Of patients with murine typhus, 64% were women, 86% were residents of Kathmandu, and 90% were unwell during the winter. No characteristics clearly distinguished typhus patients from those with blood culture–positive enteric fever

Dissemination of Spotted Fever Rickettsia Agents in Europe by Migrating Birds

Migratory birds are known to play a role as long-distance vectors for many microorganisms. To investigate whether this is true of rickettsial agents as well, we characterized tick infestation and gathered ticks from 13,260 migratory passerine birds in Sweden. A total of 1127 Ixodes spp. ticks were removed from these birds and the extracted DNA from 957 of them was available for analyses. The DNA was assayed for detection of Rickettsia spp. using real-time PCR, followed by DNA sequencing for species identification. Rickettsia spp. organisms were detected in 108 (11.3%) of the ticks. Rickettsia helvetica, a spotted fever rickettsia associated with human infections, was predominant among the PCR-positive samples. In 9 (0.8%) of the ticks, the partial sequences of 17kDa and ompB genes showed the greatest similarity to Rickettsia monacensis, an etiologic agent of Mediterranean spotted fever-like illness, previously described in southern Europe as well as to the Rickettsia sp.IrITA3 strain. For 15 (1.4%) of the ticks, the 17kDa, ompB, gltA and ompA genes showed the greatest similarity to Rickettsia sp. strain Davousti, Rickettsia japonica and Rickettsia heilongjiangensis, all closely phylogenetically related, the former previously found in Amblyomma tholloni ticks in Africa and previously not detected in Ixodes spp. ticks. The infestation prevalence of ticks infected with rickettsial organisms was four times higher among ground foraging birds than among other bird species, but the two groups were equally competent in transmitting Rickettsia species. The birds did not seem to serve as reservoir hosts for Rickettsia spp., but in one case it seems likely that the bird was rickettsiemic and that the ticks had acquired the bacteria from the blood of the bird. In conclusion, migratory passerine birds host epidemiologically important vector ticks and Rickettsia species and contribute to the geographic distribution of spotted fever rickettsial agents and their diseases

Evidence of a Louse-Borne Outbreak Involving Typhus in Douai, 1710-1712 during the War of Spanish Succession

Background: The new field of paleomicrobiology allows past outbreaks to be identified by testing dental pulp of human remains with PCR. Methods: We identified a mass grave in Douai, France dating from the early XVIII th century. This city was besieged during the European war of Spanish succession. We tested dental pulp from 1192 teeth (including 40 from Douai) by quantitative PCR (qPCR) for R. prowazekii and B. quintana. We also used ultra-sensitive suicide PCR to detect R. prowazekii and genotyped positive samples. Results and Discussion: In the Douai remains, we identified one case of B. quintana infection (by qPCR) and R. prowazekii (by suicide PCR) in 6/21 individuals (29%). The R. prowazekii was genotype B, a genotype previously found in a Spanish isolate obtained in the first part of the XX th century. Conclusion: Louse-borne outbreaks were raging during the XVIII th century; our results support the hypothesis that typhus was imported into Europe by Spanish soldiers from America

Variations of Plasmid Content in Rickettsia felis

Background: Since its first detection, characterization of R. felis has been a matter of debate, mostly due to the contamination of an initial R. felis culture by R. typhi. However, the first stable culture of R. felis allowed its precise phenotypic and genotypic characterization, and demonstrated that this species belonged to the spotted fever group rickettsiae. Later, its genome sequence revealed the presence of two forms of the same plasmid, physically confirmed by biological data. In a recent article, Gillespie et al. ( PLoS One. 2007; 2( 3): e266.) used a bioinformatic approach to refute the presence of the second plasmid form, and proposed the creation of a specific phylogenetic group for R. felis. Methodology/ Principal Findings: In the present report, we, and five independent international laboratories confirmed unambiguously by PCR the presence of two plasmid forms in R. felis strain URRWXCal(2)(T), but observed that the plasmid content of this species, from none to 2 plasmid forms, may depend on the culture passage history of the studied strain. We also demonstrated that R. felis does not cultivate in Vero cells at 37 degrees C but generates plaques at 30 degrees C. Finally, using a phylogenetic study based on 667 concatenated core genes, we demonstrated the position of R. felis within the spotted fever group. Significance: We demonstrated that R. felis, which unambiguously belongs to the spotted fever group rickettsiae, may contain up to two plasmid forms but this plasmid content is unstable

Rickettsia felis, an emerging flea-transmitted human pathogen

Rickettsia felis was first recognised two decades ago and has now been described as endemic to all continents except Antarctica. The rickettsiosis caused by R. felis is known as flea-borne spotted fever or cat-flea typhus. The large number of arthropod species found to harbour R. felis and that may act as potential vectors support the view that it is a pan-global microbe. The main arthropod reservoir and vector is the cat flea, Ctenocephalides felis, yet more than 20 other species of fleas, ticks, and mites species have been reported to harbour R. felis. Few bacterial pathogens of humans have been found associated with such a diverse range of invertebrates. With the projected increase in global temperature over the next century, there is concern that changes to the ecology and distribution of R. felis vectors may adversely impact public health